Acid Base Homeostasis in Respiration

Question 1

Identify a formula to calculate plasma pH.

Answer 1

pH = pKa + log([HCO3-] / [CO2])
where HCO3- is in mmol/L and CO2 is calculated from PCO2 and a solubility constant (40 mmHg because we are using the value of PCO2 in arterial blood)

Question 2

Define pKa.

Answer 2

pH at which 50% is ionised and 50% is unionised in the reaction.

Question 3

Write the equation corresponding to pKa for bicarbonate/carbonic acid.

Answer 3

H2CO3 ↔ HCO3- + H+
where,
50% of particles are present as H2CO3 (unionised) and 50% as HCO3- (ionised)

Question 4

Write the equilibium reaction of bicarbonate. How could we shift this to the left ? to the right ?

Answer 4

H2CO3 ↔ HCO3- + H+

If H + rises, the equation is driven to the left If H + falls, the equation is driven to the right

Question 5

What is the pKa of bircarbonate ? What is normal pH ?

Answer 5

pKa for bicarbonate/carbonic acid: 6.1

normal pH = 7.4

Question 6

At normal pH is there more bicarbonate, or more carbonic acid ?

Answer 6

6.1 is pH where 50% carbonic acid and 50% bicarbonate. Decreasing H+ (i.e. increasing pH to 7.4) would shift the equilibrium to the right in this equation:
H2CO3 ↔ HCO3- + H+
so there would be more bicarbonate in normal pH.

Question 7

What is the ratio of bicarbonate to carbonic acid at pH 7.4 ?

Answer 7

pH = pKa + log ([H+][A-]:[HA])

7.4 = 6.1 + log ([bicarbonate]/[carbonic acid])
1 = log ([bicarbonate]/[carbonic acid])
reverse log (1) = bicarbonate / carbonic acid
bicarbonate / carbonic acid = 10

Question 8

How can we change absolute levels of bicarbonate ?

Answer 8

The absolute levels of bicarbonate can be changed by changes to breathing.
Given that H2O + CO2 → H2CO3, increased CO2 leads to more H2CO3.
This increase in H2CO3 in turn leads to an increase in bicarbonate. Vice versa.

Question 9

Write the equation for the bicarbonate buffer system ? Show where respiratory, and metabolic disturbances affect the equation.

Answer 9

CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-

• If disturbance in CO2, respiratory disturbances
• If disturbance in H+ or HCO3, metabolic disturbance s

Question 10

Define acidosis and alkalosis.

Answer 10

pH < 7.35 acidosis

pH >7.45 alkalosis

Question 11

Draw a Davenport diagram, and explain its contents.

Answer 11

Refer to slide 8 in lecture on “Acid Base Homeostasis”
AB shows plasma pH change as CO2 changes
CD shows plasma pH change when non-volatile acid is added/ removed (static PCO2)

Line at concentration of HCO3- at 24 mmol/l
is the buffer line

Question 12

Identify the main kinds of acid-base disturbances. What are the main causes of each of these acid-base disturbances ?

Answer 12

RESPIRATORY DISORDERS (alkalosis and acidosis)
☺ Increased CO2 (hypoventilate)
☺ Decreased CO2 (hyperventilate)

METABOLIC DISORDERS (alkalosis and acidosis) 
☺ Increased non-volatile acid/decreased base
☺ Increased base/decreased non-volatile acid

ALKALOSES (can be respiratory or metabolic)
♦ Fall in PCO2
♦ Rise in HCO3-

ACIDOSES (can be respiratory or metabolic)
♦ Rise in PCO2
♦ Fall in HCO3-

Question 13

In general, how does the body respond to alkaloses or acidoses ?

Answer 13

♠ The lungs and kidneys may try to return any disturbance towards normal (i.e. back to pH 7.4) – compensation.

♠ Two ways:

1. the respiratory system alters ventilation – (happens quickly)
2. the kidneys alter excretion of bicarbonate – (takes 2-3 days)

Question 14

Identify the main causes of respiratory acidosis.

Answer 14

♣ Results from an increase in PCO2 caused by:

• Hypoventilation (less CO2 being blown away)
• Ventilation:perfusion mismatch

♣ This can specifically be due to:

• COPD
• Blocked airway (tumour or foreign body)
• Lung collapse
• Injury to chest wall
• Drugs reducing respiratory drive (e.g. morphine, barbituates, general anaesthetics)

♣ From Henderson-Hasselbach equation, an increase in PCO2 causes an increase in H+, so a lowering of pH.

Question 15

Explain the compensation which occurs as a result of respiratory acidosis.

Answer 15

♣ Compensation occurs through

a) “Plasma HCO3- levels increase to compensate for increased H+ concentration (i.e. increased [HCO3-] will counteract the effect on the pH of an increased pCO2 because it returns the value of the [HCO3]/0.03 PCO2 ratio towards normal)”
b) Renal compensation – increased HCO3- reabsorption and increased HCO3- production raises pH towards normal (but pH return often incomplete)

Question 16

Identify the main causes of respiratory alkalosis.

Answer 16

• Results from a decrease in PCO2, generally caused by alveolar hyperventilation (more CO2 being blown away).

• This can specifically be due to:
- Increased ventilation, from hypoxic drive in pneumonia, diffuse interstitial lung
diseases, high altitude, mechanical ventilation
- Hyperventilation – brainstem damage, infection driving fever.

• From Henderson-Hasselbach equation, an decrease in PCO2 causes an decrease in H+, so a rise of pH.

Question 17

Explain the compensation which occurs as a result of respiratory alkalosis.

Answer 17

a) “Plasma HCO3- levels decrease to compensate for decreased H+ concentration (i.e. decreased [HCO3-] will counteract the effect on the pH of a decreased pCO2 because it returns the value of the [HCO3]/0.03 PCO2 ratio towards normal)”

b) Renal compensation – reduced HCO3- reabsorption, and reduced HCO3-
production. Thus plasma HCO3- levels fall, compensating for lower H+ (but leaving base deficit, i.e. low bicarbonate), moving pH back towards normal.

Question 18

Identify the main causes of metabolic acidosis.

Answer 18

• Results from an excess of H+ in the body, which reduces HCO3 levels (shifts equation to the left). Respiration is unaffected, therefore PCO2 is initially normal.
• This can specifically be due to:
• Loss of HCO3- (e.g. from gut in diarrhoea)
• Exogenous acid overloading (e.g. aspirin overdose), endogenous acid production (e.g. ketogenesis for instance in diabetes mellitus)
• Failure to secrete H+ (e.g. renal failure)

Question 19

Explain the compensation which occurs as a result of metabolic acidosis.

Answer 19

a) Bicarbonate equation is driven further to the left, lowering H+ and HCO3-
concentration further. The decrease in H+ concentration moves pH towards normal.

b) Respiratory compensation – the lower pH is detected by peripheral chemoreceptors,
causes an increase in ventilation which lowers PCO2.
Respiratory compensation cannot fully correct the pH, HCO3 and H+, so excess H+ needs to be removed or HCO3- restored by c)

c) Slow renal compensation

There remains a base deficit (i.e. low bicarbonate levels).

Question 20

Are respiratory and metabolic compensations 100% ?

Answer 20

NO

Question 21

Identify the main causes of metabolic alkalosis.

Answer 21

• Results from an increase in HCO3- concentration or a fall in H+. Removing H+ from equation drives reaction to right, increases HCO3- (i.e. base excess exists). Lowering of H+ raises pH, with PCO2 initially being normal.
• This can specifically be due to:
• Vomiting (i.e. loss of HCl from stomach)
• Ingestion of alkali substances
• Potassium depletion (e.g. diuretics)

Question 22

Explain the compensation which occurs as a result of metabolic alkalosis.

Answer 22

a) Equation is driven further to right, increasing H+ and HCO3-. Increase in H+ moves pH towards normal.
b) Respiratory compensation (often small or sometimes absent)– increase in pH detected by peripheral chemoreceptors decreases ventilation which raises PCO2. Respiratory compensation is often small (or even absent) – ventilation cannot reduce enough to correct imbalance. Hence c)
c) Renal response is to secrete less H+

Overall, base excess is exacerbated.

Question 23

What is meant by non-volatile, in “increased non-volatile acid” in Davenport diagrams ?

Answer 23

Means increases in H+ (volatile part is carbonic acid).

Question 24

Draw a Davenport diagram for respiratory acidosis and alkalosis, explaining the main features of the diagram.

Answer 24

Refer to slide 13 in lecture on “Acid-base homeostasis”

1) Respiratory acidosis
- Normal to point A: Increased CO2 has led to both an increase in HCO3- and H+ (↓pH)
- Renal compensation moves pH back to normal (i.e. point B, but at higher plasma HCO3- than normal) by secreting less bicarbonate to buffer the extra H+ and by excreting more acid
- PCO2 has not changed during compensation (60 mmHg the whole time, normal is 40 mmHg)

2) Respiratory alkalosis
- Normal to point C: decreased CO2 leads to both a decrease in HCO3- and H+ (↑pH)
- Renal compensation moves pH back to normal (i.e. point D, but at lower plasma HCO3- than normal) by secreting less H+ and excreting more bicarbonate
- PCO2 has not changed during compensation (25 mmHg the whole time, normal is 40 mmHg)

Question 25

Draw a Davenport diagram for metabolic acidosis and alkalosis, explaining the main features of the diagram.

Answer 25

Refer to slide 18 in lecture on “Acid-base homeostasis”

1) Metabolic acidosis
- Normal to point A: Loss of base/ gain of acid (H+) makes plasma more acidic (↓pH)
- Respiratory compensation: blow off CO2 (through increase in respiration)
- PCO2 initially normal (at point A), but respiratory compensation (seconds to minutes, A to B) causes it to fall from 40 mmHg to 25 mmHg.
- Full metabolic (renal) compensation is not shown (hours to days)

2) Metabolic alkalosis
- Normal to point C: Loss of acid (H+)/ gain of base makes plasma more alkaline
- Respiratory compensation: retain CO2 (through depressed respiration, can be impossible if patient can no longer reduce breathing)
- PCO2 initially normal (at point C), but respiratory compensation (seconds to minutes, C to D) causes it to increase from 40 mmHg to 60 mmHg.
- Full metabolic (renal) compensation is not shown (hours to days)

Compensation for both of these tends to not be able to return to normal pH completely!!